Hypothyroidism

Abstract

We would add to Lindsay and Toft's1Lindsay RS Toft AD Hypothyroidism.Lancet. 1997; 349: 413-417Summary Full Text Full Text PDF PubMed Scopus (55) Google Scholar review of the major causes of hypothyroidism. Subclinical hypothyroidism is commonly encountered in cystic fibrosis (CF) and may soon become a clinically relevant problem because the survival rate of CF patients is now considerably increased. Goitres with or without hypothyroidism in CF patients were reported in the early 1970s but were related to the chronic ingestion of iodide-containing expectorant. However, in more recent studies, a status of subclinical hypothyroidism was defined in CF patients on the basis of normal (though sometimes raised) TSH but always accompanied by an increased thyrotropin secretory response to thyrotropin releasing hormone (TRH).2DeLuca F.Trimarchi F Sferlazzas C et al.Thyroid function in children with cystic fibrosis.Eur J Pediatr. 1982; 138: 327-330Crossref PubMed Scopus (24) Google Scholar We have shown that the product of the CF gene, the cystic fibrosis transmembrane conductance regulator (CFTR), is indeed expressed in human thyroid3Devuyst O, Colstein PE, Sanches MV, et al. Expression of CFTR in human and bovine thyroid epithelium. Am J Physiol (in press).Google Scholar thus providing a molecular basis for possible dysfunction when the gene is mutated. The level of CFTR expression in a particular organ may of course not directly reflect the degree of involvement of that organ in CF patients. For instance, although CFTR is abundantly expressed in the kidney,4Crawford L Maloney PC Zeitlin PL et al.Immunocytochemical localisation of the cystic fibrosis gene product CFTR.Proc Natl Acad Sci USA. 1991; 88: 9262-9266Crossref PubMed Scopus (393) Google Scholar there is no classic renal phenotype in CF. This finding contrasts with a low level of CFTR expression in bronchial epithelium, which is the major site of morbidity.4Crawford L Maloney PC Zeitlin PL et al.Immunocytochemical localisation of the cystic fibrosis gene product CFTR.Proc Natl Acad Sci USA. 1991; 88: 9262-9266Crossref PubMed Scopus (393) Google Scholar Thus specific protective mechanisms could be operating and account for the variability in organ dysfunction. For example, since CFTR functions mainly as a chloride channel, the severity of the disease in an organ will be determined by the activity of other types of chloride channels. In any event, the precise role of CFTR in thyroid physiology is not yet established, but our study points to a role in colloid chloride secretion and overall in follicle enlargement, as proposed for renal cysts in autosomal dominant polycystic kidney disease.5Hanaoka K Devuyst O Schwiebert EM Wilson PD. Guggino WB A role for CFTR in human autosomal dominant polycystic kidney disease.Am J Phyiol. 1996; 270: C389-C399PubMed Google Scholar Careful post-mortem thyroid examination should reveal whether or not the mean size of thyroid follicle is indeed smaller in CF patients.